Small molecule shows first-in-human MoA for salivary gland cancers

SuviCa (University of Colorado-Bolder)

SVC112 is a late-preclinical stage asset with potent single agent activity in genetically-defined models of salivary gland cancer, a neglected and orphan disease with no approved targeted or immunotherapy agents.

SVC112 is a small synthetic molecule that reversibly inhibits translation Elongation Factor 2 by a first-in-human mechanism. SVC112 offers an opportunity to overcome two persistent barriers in effective and enduring cancer therapy: the challenge in drugging oncogenic transcription factors such as Myc and Myb that lack biochemical activity (e.g. kinase activity) and the need to target multiple oncogenic proteins simultaneously in order to avoid acquired resistance to single-target agents (e.g. BRAF inhibitors). SVC112 depletes multiple hard-to-drug oncogenic drivers of salivary gland cancer simultaneously, overcoming both barriers.

Salivary gland cancer (SGC) is a neglected orphan disease with no approved targeted or immunotherapy agents. SVC112 exhibits robust single agent activity in Myb-fusion and Myb-overexpressing SGC PDX models, with no sign of clinical toxicity at therapeutic doses. SVC112 outperforms standard-of-care in side-by-side testing. SVC112 is more potent in cancer cells over normal cells in vitro, promising better therapeutic index than the only FDA-approved inhibitor of translation elongation in the clinic.

SuviCa holds an exclusive license for composition of matter patents for SVC112. With non-dilutive funds from Phase I/II NCI SBIRs, SuviCa has amassed substantial preclinical data on SVC112, including: SAR; complete synthesis and scale up; single and repeat dose rodent tox; rodent and dog PK; PK/PD relationship in tumor-bearing mice; efficacy in multiple PDX models; prospective PD biomarkers in circulating blood cells; and a clinically applicable injectable formulation. University of Colorado Cancer Center clinicians are on board to conduct Investigator-Initiated Clinical Trials. We seek funds for GLP-tox/GMP synthesis, to file an IND.